The objectives of this project are to study immunopathogenesis and kinetics of the human immune response to gonococcal disease. Gonorrhea is a major public health problem with over 2 million reported cases per year. Infection in females can lead to serious complications such as pelvic inflammatory disease (PID) with public health costs estimated at $4 billion dollars per year. To design intervention strategies, more information is needed about the immune response to gonorrhea. This project provides the opportunity to assess the immune response in experimental infections in a male challenge model, in acute infections in males and females at an STD clinic, and in an experimental female mouse model. Specific aims are to characterize early and acute phase human response to infection, to determine if postinfection immunity affects subsequent reinfection, and to assess genital tract immunology in a mouse model. The humoral and cellular immune parameters to gonococcal infection will be characterized in two settings. The first is experimental infection of men by intraurethral challenge. The second is acute infection in males and females at the Baltimore City STD clinics. To examine postinfection acquired immunity in the male challenge model, we will rechallenge previously infected volunteers with the same challenge strain. To examine naturally acquired disease, a nested case control study of STD patients at the Baltimore City clinic will be conducted. The clinical core will collect, catalog, and store serum and strains from male and female patients, and cervical/vaginal lavages from females. Retrospectively, patients will be selected based on histories to examine the effect of prior immunological status on reinfection with gonorrhea. The final aim is to immunology of the genital tract in animals with the goal of optimizing and characterizing a transient infection in the mouse vagina as a potential model. If feasible, this system could be utilized to test passive immunoprophylaxis and active immunization.